Reduced lopinavir exposure during pregnancy

Background: Optimal antiretroviral exposure during pregnancy is critical for prevention of mother-to-child HIV transmission and for maternal health. Pregnancy can alter antiretroviral pharmacokinetics. Our objective was to describe lopinavir/ritonavir (LPV/r) pharmacokinetics during pregnancy. Methods: We performed intensive steady-state 12-h pharmacokinetic profiles of lopinavir and ritonavir (three capsules: LPV 400 mg/r 100 mg) at 30-36 weeks gestation and 6-12 weeks postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured LPV and ritonavir by reverse-phase high-performance liquid chromatography. Target LPV area under concentration versus time curve (AUC) was >= 52 mu g h/ml, the estimated 10th percentile LPV AUC in non-pregnant historical controls (mean AUC = 83 mu g h/ml). Results: Seventeen women completed antepartum evaluations; average gestational age was 35 weeks. Geometric mean antepartum LPV AUC was 44.4 mu g h/ml [90% confidence interval (CI), 38.7-50.9] and 12-h post-dose concentration (C-12h) was 1.6 mu g/ml (90% CI, 1.1-2.5). Twelve women completed postpartum evaluations; geometric mean LPV AUC was 65.2 mu g h/ml (90% CI, 49.7-85.4) and C-12h was 4.6 mu g/ml (90% CI, 3.7-5.7). The geometric mean ratio of antepartum/postpartum LPV AUC was 0.72 (90% CI, 0.54-0.96). Fourteen of 17 (82%) pregnant and three of 12 (25%) postpartum women did not meet our target LPV AUC. The ratio of cord blood/ maternal LPV concentration in ten paired detectable samples was 0.2 +/- 0.13. Conclusions: LPV/r exposure during late pregnancy was lower compared to postpartum and compared to non-pregnant historical controls. Small amounts of lopinavir cross the placenta. The pharmacokinetics, safety, and effectiveness of increased LPV/r dosing during the third trimester of pregnancy should be investigated. (c) 2006 Lippincott Williams & Wilkins.